排序方式: 共有27条查询结果,搜索用时 15 毫秒
1.
Amundadottir LT Sulem P Gudmundsson J Helgason A Baker A Agnarsson BA Sigurdsson A Benediktsdottir KR Cazier JB Sainz J Jakobsdottir M Kostic J Magnusdottir DN Ghosh S Agnarsson K Birgisdottir B Le Roux L Olafsdottir A Blondal T Andresdottir M Gretarsdottir OS Bergthorsson JT Gudbjartsson D Gylfason A Thorleifsson G Manolescu A Kristjansson K Geirsson G Isaksson H Douglas J Johansson JE Bälter K Wiklund F Montie JE Yu X Suarez BK Ober C Cooney KA Gronberg H Catalona WJ Einarsson GV 《Nature genetics》2006,38(6):652-658
With the increasing incidence of prostate cancer, identifying common genetic variants that confer risk of the disease is important. Here we report such a variant on chromosome 8q24, a region initially identified through a study of Icelandic families. Allele -8 of the microsatellite DG8S737 was associated with prostate cancer in three case-control series of European ancestry from Iceland, Sweden and the US. The estimated odds ratio (OR) of the allele is 1.62 (P = 2.7 x 10(-11)). About 19% of affected men and 13% of the general population carry at least one copy, yielding a population attributable risk (PAR) of approximately 8%. The association was also replicated in an African American case-control group with a similar OR, in which 41% of affected individuals and 30% of the population are carriers. This leads to a greater estimated PAR (16%) that may contribute to higher incidence of prostate cancer in African American men than in men of European ancestry. 相似文献
2.
Stacey SN Gudbjartsson DF Sulem P Bergthorsson JT Kumar R Thorleifsson G Sigurdsson A Jakobsdottir M Sigurgeirsson B Benediktsdottir KR Thorisdottir K Ragnarsson R Scherer D Rudnai P Gurzau E Koppova K Höiom V Botella-Estrada R Soriano V Juberías P Grasa M Carapeto FJ Tabuenca P Gilaberte Y Gudmundsson J Thorlacius S Helgason A Thorlacius T Jonasdottir A Blondal T Gudjonsson SA Jonsson GF Saemundsdottir J Kristjansson K Bjornsdottir G Sveinsdottir SG Mouy M Geller F Nagore E Mayordomo JI 《Nature genetics》2008,40(11):1313-1318
To search for new sequence variants that confer risk of cutaneous basal cell carcinoma (BCC), we conducted a genome-wide SNP association study of 930 Icelanders with BCC and 33,117 controls. After analyzing 304,083 SNPs, we observed signals from loci at 1p36 and 1q42, and replicated these associations in additional sample sets from Iceland and Eastern Europe. Overall, the most significant signals were from rs7538876 on 1p36 (OR = 1.28, P = 4.4 x 10(-12)) and rs801114 on 1q42 (OR = 1.28, P = 5.9 x 10(-12)). The 1p36 locus contains the candidate genes PADI4, PADI6, RCC2 and ARHGEF10L, and the gene nearest to the 1q42 locus is the ras-homolog RHOU. Neither locus was associated with fair pigmentation traits that are known risk factors for BCC, and no risk was observed for melanoma. Approximately 1.6% of individuals of European ancestry are homozygous for both variants, and their estimated risk of BCC is 2.68 times that of noncarriers. 相似文献
3.
Sulem P Gudbjartsson DF Walters GB Helgadottir HT Helgason A Gudjonsson SA Zanon C Besenbacher S Bjornsdottir G Magnusson OT Magnusson G Hjartarson E Saemundsdottir J Gylfason A Jonasdottir A Holm H Karason A Rafnar T Stefansson H Andreassen OA Pedersen JH Pack AI de Visser MC Kiemeney LA Geirsson AJ Eyjolfsson GI Olafsson I Kong A Masson G Jonsson H Thorsteinsdottir U Jonsdottir I Stefansson K 《Nature genetics》2011,43(11):1127-1130
We tested 16 million SNPs, identified through whole-genome sequencing of 457 Icelanders, for association with gout and serum uric acid levels. Genotypes were imputed into 41,675 chip-genotyped Icelanders and their relatives, for effective sample sizes of 968 individuals with gout and 15,506 individuals for whom serum uric acid measurements were available. We identified a low-frequency missense variant (c.1580C>G) in ALDH16A1 associated with gout (OR = 3.12, P = 1.5 × 10(-16), at-risk allele frequency = 0.019) and serum uric acid levels (effect = 0.36 s.d., P = 4.5 × 10(-21)). We confirmed the association with gout by performing Sanger sequencing on 6,017 Icelanders. The association with gout was stronger in males relative to females. We also found a second variant on chromosome 1 associated with gout (OR = 1.92, P = 0.046, at-risk allele frequency = 0.986) and serum uric acid levels (effect = 0.48 s.d., P = 4.5 × 10(-16)). This variant is close to a common variant previously associated with serum uric acid levels. This work illustrates how whole-genome sequencing data allow the detection of associations between low-frequency variants and complex traits. 相似文献
4.
Respiration as the main determinant of carbon balance in European forests 总被引:106,自引:0,他引:106
Valentini R Matteucci G Dolman AJ Schulze ED Rebmann C Moors EJ Granier A Gross P Jensen NO Pilegaard K Lindroth A Grelle A Bernhofer C Grünwald T Aubinet M Ceulemans R Kowalski AS Vesala T Rannik U Berbigier P Loustau D Gudmundsson J Thorgeirsson H Ibrom A Morgenstern K Clement R 《Nature》2000,404(6780):861-865
Carbon exchange between the terrestrial biosphere and the atmosphere is one of the key processes that need to be assessed in the context of the Kyoto Protocol. Several studies suggest that the terrestrial biosphere is gaining carbon, but these estimates are obtained primarily by indirect methods, and the factors that control terrestrial carbon exchange, its magnitude and primary locations, are under debate. Here we present data of net ecosystem carbon exchange, collected between 1996 and 1998 from 15 European forests, which confirm that many European forest ecosystems act as carbon sinks. The annual carbon balances range from an uptake of 6.6 tonnes of carbon per hectare per year to a release of nearly 1 t C ha(-1) yr(-1), with a large variability between forests. The data show a significant increase of carbon uptake with decreasing latitude, whereas the gross primary production seems to be largely independent of latitude. Our observations indicate that, in general, ecosystem respiration determines net ecosystem carbon exchange. Also, for an accurate assessment of the carbon balance in a particular forest ecosystem, remote sensing of the normalized difference vegetation index or estimates based on forest inventories may not be sufficient. 相似文献
5.
Gretarsdottir S Thorleifsson G Reynisdottir ST Manolescu A Jonsdottir S Jonsdottir T Gudmundsdottir T Bjarnadottir SM Einarsson OB Gudjonsdottir HM Hawkins M Gudmundsson G Gudmundsdottir H Andrason H Gudmundsdottir AS Sigurdardottir M Chou TT Nahmias J Goss S Sveinbjörnsdottir S Valdimarsson EM Jakobsson F Agnarsson U Gudnason V Thorgeirsson G Fingerle J Gurney M Gudbjartsson D Frigge ML Kong A Stefansson K Gulcher JR 《Nature genetics》2003,35(2):131-138
We previously mapped susceptibility to stroke to chromosome 5q12. Here we finely mapped this locus and tested it for association with stroke. We found the strongest association in the gene encoding phosphodiesterase 4D (PDE4D), especially for carotid and cardiogenic stroke, the forms of stroke related to atherosclerosis. Notably, we found that haplotypes can be classified into three distinct groups: wild-type, at-risk and protective. We also observed a substantial disregulation of multiple PDE4D isoforms in affected individuals. We propose that PDE4D is involved in the pathogenesis of stroke, possibly through atherosclerosis, which is the primary pathological process underlying ischemic stroke. 相似文献
6.
Gudmundur Gudmundsson 《Journal of forecasting》1999,18(1):33-37
Various methods based on smoothing or statistical criteria have been used for constructing disaggregated values compatible with observed annual totals. The present method is based on a time‐series model in a state space form and allows for a prescribed multiplicative trend. It is applied to US GNP data which have been used for comparing methods suggested for this purpose. The model can be extended to include quarterly series, related to the unknown disaggregated values. But as the estimation criteria are based on prediction errors of the aggregated values, the estimated form may not be optimal for reproducing high‐frequency variations of the disaggregated values. Copyright © 1999 John Wiley & Sons, Ltd. 相似文献
7.
Helgadottir A Manolescu A Helgason A Thorleifsson G Thorsteinsdottir U Gudbjartsson DF Gretarsdottir S Magnusson KP Gudmundsson G Hicks A Jonsson T Grant SF Sainz J O'Brien SJ Sveinbjornsdottir S Valdimarsson EM Matthiasson SE Levey AI Abramson JL Reilly MP Vaccarino V Wolfe ML Gudnason V Quyyumi AA Topol EJ Rader DJ Thorgeirsson G Gulcher JR Hakonarson H Kong A Stefansson K 《Nature genetics》2006,38(1):68-74
Variants of the gene ALOX5AP (also known as FLAP) encoding arachidonate 5-lipoxygenase activating protein are known to be associated with risk of myocardial infarction. Here we show that a haplotype (HapK) spanning the LTA4H gene encoding leukotriene A4 hydrolase, a protein in the same biochemical pathway as ALOX5AP, confers modest risk of myocardial infarction in an Icelandic cohort. Measurements of leukotriene B4 (LTB4) production suggest that this risk is mediated through upregulation of the leukotriene pathway. Three cohorts from the United States also show that HapK confers a modest relative risk (1.16) in European Americans, but it confers a threefold larger risk in African Americans. About 27% of the European American controls carried at least one copy of HapK, as compared with only 6% of African American controls. Our analyses indicate that HapK is very rare in Africa and that its occurrence in African Americans is due to European admixture. Interactions with other genetic or environmental risk factors that are more common in African Americans are likely to account for the greater relative risk conferred by HapK in this group. 相似文献
8.
Two variants on chromosome 17 confer prostate cancer risk, and the one in TCF2 protects against type 2 diabetes 总被引:1,自引:0,他引:1
Gudmundsson J Sulem P Steinthorsdottir V Bergthorsson JT Thorleifsson G Manolescu A Rafnar T Gudbjartsson D Agnarsson BA Baker A Sigurdsson A Benediktsdottir KR Jakobsdottir M Blondal T Stacey SN Helgason A Gunnarsdottir S Olafsdottir A Kristinsson KT Birgisdottir B Ghosh S Thorlacius S Magnusdottir D Stefansdottir G Kristjansson K Bagger Y Wilensky RL Reilly MP Morris AD Kimber CH Adeyemo A Chen Y Zhou J So WY Tong PC Ng MC Hansen T Andersen G Borch-Johnsen K Jorgensen T Tres A Fuertes F 《Nature genetics》2007,39(8):977-983
We performed a genome-wide association scan to search for sequence variants conferring risk of prostate cancer using 1,501 Icelandic men with prostate cancer and 11,290 controls. Follow-up studies involving three additional case-control groups replicated an association of two variants on chromosome 17 with the disease. These two variants, 33 Mb apart, fall within a region previously implicated by family-based linkage studies on prostate cancer. The risks conferred by these variants are moderate individually (allele odds ratio of about 1.20), but because they are common, their joint population attributable risk is substantial. One of the variants is in TCF2 (HNF1beta), a gene known to be mutated in individuals with maturity-onset diabetes of the young type 5. Results from eight case-control groups, including one West African and one Chinese, demonstrate that this variant confers protection against type 2 diabetes. 相似文献
9.
Thorgeirsson TE Geller F Sulem P Rafnar T Wiste A Magnusson KP Manolescu A Thorleifsson G Stefansson H Ingason A Stacey SN Bergthorsson JT Thorlacius S Gudmundsson J Jonsson T Jakobsdottir M Saemundsdottir J Olafsdottir O Gudmundsson LJ Bjornsdottir G Kristjansson K Skuladottir H Isaksson HJ Gudbjartsson T Jones GT Mueller T Gottsäter A Flex A Aben KK de Vegt F Mulders PF Isla D Vidal MJ Asin L Saez B Murillo L Blondal T Kolbeinsson H Stefansson JG Hansdottir I Runarsdottir V Pola R Lindblad B 《Nature》2008,452(7187):638-642
Smoking is a leading cause of preventable death, causing about 5 million premature deaths worldwide each year. Evidence for genetic influence on smoking behaviour and nicotine dependence (ND) has prompted a search for susceptibility genes. Furthermore, assessing the impact of sequence variants on smoking-related diseases is important to public health. Smoking is the major risk factor for lung cancer (LC) and is one of the main risk factors for peripheral arterial disease (PAD). Here we identify a common variant in the nicotinic acetylcholine receptor gene cluster on chromosome 15q24 with an effect on smoking quantity, ND and the risk of two smoking-related diseases in populations of European descent. The variant has an effect on the number of cigarettes smoked per day in our sample of smokers. The same variant was associated with ND in a previous genome-wide association study that used low-quantity smokers as controls, and with a similar approach we observe a highly significant association with ND. A comparison of cases of LC and PAD with population controls each showed that the variant confers risk of LC and PAD. The findings provide a case study of a gene-environment interaction, highlighting the role of nicotine addiction in the pathology of other serious diseases. 相似文献
10.
Gudbjartsson DF Arnar DO Helgadottir A Gretarsdottir S Holm H Sigurdsson A Jonasdottir A Baker A Thorleifsson G Kristjansson K Palsson A Blondal T Sulem P Backman VM Hardarson GA Palsdottir E Helgason A Sigurjonsdottir R Sverrisson JT Kostulas K Ng MC Baum L So WY Wong KS Chan JC Furie KL Greenberg SM Sale M Kelly P MacRae CA Smith EE Rosand J Hillert J Ma RC Ellinor PT Thorgeirsson G Gulcher JR Kong A Thorsteinsdottir U Stefansson K 《Nature》2007,448(7151):353-357
Atrial fibrillation (AF) is the most common sustained cardiac arrhythmia in humans and is characterized by chaotic electrical activity of the atria. It affects one in ten individuals over the age of 80 years, causes significant morbidity and is an independent predictor of mortality. Recent studies have provided evidence of a genetic contribution to AF. Mutations in potassium-channel genes have been associated with familial AF but account for only a small fraction of all cases of AF. We have performed a genome-wide association scan, followed by replication studies in three populations of European descent and a Chinese population from Hong Kong and find a strong association between two sequence variants on chromosome 4q25 and AF. Here we show that about 35% of individuals of European descent have at least one of the variants and that the risk of AF increases by 1.72 and 1.39 per copy. The association with the stronger variant is replicated in the Chinese population, where it is carried by 75% of individuals and the risk of AF is increased by 1.42 per copy. A stronger association was observed in individuals with typical atrial flutter. Both variants are adjacent to PITX2, which is known to have a critical function in left-right asymmetry of the heart. 相似文献